Drugs
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Chronic post-surgical pain (CPSP) is a serious complication of major surgery that can impair a patient's quality of life. The development of CPSP is a complex process which involves biologic, psychosocial, and environmental mechanisms that have yet to be fully understood. ⋯ This article reviews the main pharmacologic candidates for the treatment of CPSP, discusses the future of preventive analgesia, and considers novel strategies to help treat acute post-operative pain and lessen the risk that it becomes chronic. In addition, this article highlights important areas of focus for clinical practice including: multimodal management of CPSP patients, psychological modifiers of the pain experience, and the development of a Transitional Pain Service specifically designed to manage patients at high risk of developing chronic post-surgical pain.
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Fluticasone furoate/vilanterol (Relvar(®)) is a once-daily, fixed combination of an inhaled corticosteroid (ICS) and a long-acting β2-adrenoreceptor agonist (LABA), delivered via a dry powder inhaler (Ellipta(®)). It is approved for the treatment of asthma in the EU and Japan, and is the first once-daily ICS/LABA to be available for this indication. Fluticasone furoate is an enhanced-affinity glucocorticoid receptor agonist, with potent anti-inflammatory activity. ⋯ In clinical trials, fluticasone furoate/vilanterol was generally well tolerated with fewer than 15 % of patients experiencing treatment-related adverse events, the most common of which were oral/oropharyngeal candidiasis, dysphonia, extrasystoles and cough. The tolerability profile of fluticasone furoate/vilanterol was generally similar to that of fluticasone propionate/salmeterol. Thus, fluticasone furoate/vilanterol is an effective and generally well tolerated ICS/LABA option for the treatment of uncontrolled asthma.
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Pirfenidone (Esbriet®) is an orally administered, synthetic, pyridone compound that is approved for the treatment of adults with mild to moderate idiopathic pulmonary fibrosis (IPF) in the EU, and for the treatment of IPF in the USA. This article summarizes pharmacological, efficacy and tolerability data relevant to the use of pirfenidone in these indications. In the randomized, double-blind, placebo-controlled, multinational CAPACITY trials in patients with mild to moderate IPF, a significant reduction in the rate of decline in forced vital capacity (FVC) was seen with pirfenidone versus placebo in study 004 but not in study 006. ⋯ Gastrointestinal and skin-related events (e.g. nausea, rash, photosensitivity reaction), which were the most commonly occurring treatment-emergent adverse events, were generally mild to moderate in severity. In addition, a prespecified mortality analysis across all three studies demonstrated a significant reduction in IPF-related and all-cause mortality with pirfenidone. In conclusion, oral pirfenidone is a valuable agent for use in patients with IPF.
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Tedizolid phosphate is a novel oxazolidinone prodrug (converted to the active form tedizolid by phosphatases in vivo) that has been developed and recently approved (June 2014) by the United States FDA for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Tedizolid is an oxazolidinone, but differs from other oxazolidinones by possessing a modified side chain at the C-5 position of the oxazolidinone nucleus which confers activity against certain linezolid-resistant pathogens and has an optimized C- and D-ring system that improves potency through additional binding site interactions. The mechanism of action of tedizolid is similar to other oxazolidinones and occurs through inhibition of bacterial protein synthesis by binding to 23S ribosomal RNA (rRNA) of the 50S subunit of the ribosome. ⋯ Tyramine and pseudoephedrine challenge studies in humans have also reported no meaningful MAO-related interactions with tedizolid. With its enhanced in vitro activity against a broad-spectrum of Gram-positive aerobic bacteria, convenient once-daily dosing, a short 6-day course of therapy, availability of both oral and intravenous routes of administration, and an adverse effect profile that appears to be more favorable than linezolid, tedizolid is an attractive agent for use in both the hospital and community settings. Tedizolid is currently undergoing additional Phase III clinical trials for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilated nosocomial pneumonia (VNP).
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Delamanid (Deltyba(®)), a nitroimidazo-oxazole derivative, is a new anti-tuberculosis (TB) drug which exhibits potent in vitro and in vivo antitubercular activity against drug-susceptible and -resistant strains of Mycobacterium tuberculosis. It is approved in several countries, including Japan and those of the EU, for use as part of an appropriate combination regimen in adults with multidrug-resistant tuberculosis (MDR-TB) when an effective treatment regimen cannot otherwise be composed due to resistance or tolerability. In a robust phase II trial in adult patients with MDR-TB, oral delamanid 100 mg twice daily for 2 months plus an optimized background regimen improved sputum culture conversion rates to a significantly greater extent than placebo. ⋯ Delamanid was generally well tolerated in patients with MDR-TB, with gastrointestinal adverse events and insomnia reported most commonly. Although the incidence of QT interval prolongation was higher with delamanid-based therapy, it was not associated with clinical symptoms such as syncope and arrhythmia. In conclusion, delamanid is a useful addition to the treatment options currently available for patients with MDR-TB.